Effects of combination therapy with amlodipine and fosinopril administered at different times on blood pressure and circadian blood pressure pattern in patients with essential hypertension.

The objective of our study was to compare the effects of a combination therapy with amlodipine and fosinopril administered concomitantly or at different times on blood pressure and circadian blood pressure pattern in subjects with essential hypertension. 40 subjects with grade 1-2 essential hypertension and uncontrolled blood pressure after amlodipine or fosinopril monotherapy were randomized to combination therapy with amlodipine and fosinopril given in the morning and at bedtime (group A), or given concomitantly in the morning (group B). Clinic blood pressure values and 24-hour ambulatory blood pressure measurements were obtained before and after 4 weeks of treatment. After treatment, a reduction of 24-hour mean systolic and diastolic blood pressure was found in both groups. Subjects in group A showed a significant reduction in mean nocturnal systolic and diastolic blood pressure compared with group B (22.38/17.39 mmHg vs. 7.61/6.32 mmHg; P < 0.001). In group A a significant increase (5.68% and 4.57%, respectively; P < 0.05) was found in the diurnal/nocturnal blood pressure ratios of systolic and diastolic blood pressure and a slight reduction in the prevalence of non-dipping (< 10% decline in mean nocturnal vs. diurnal BP) from 53.85% to 30.77% (P = 0.428). Group B showed a significant reduction (5.68% and 5.76%; P < 0.01) in the diurnal/nocturnal systolic and diastolic blood pressure ratios and a slight increase in the prevalence of non-dipping from 38.46% to 53.85% (P = 0.428). Compared to concomitant administration of amlodipine and fosinopril in the morning, administration of the drugs at different times significantly decreased nocturnal blood pressure, increased the diurnal/nocturnal blood pressure ratio, and normalized the circadian blood pressure pattern. These findings indicate that chronotherapy may be an important strategy for optimizing blood pressure control and restoring the circadian blood pressure pattern.